PROJECT SUMMARY/ABSTRACT This application describes a five-year training program for development of an academic career in studying the role of skin-derived BDNF in the maintenance and protection of cutaneous mechanosensory afferents. I am a physician scientist with an expertise in neuropathology. I will establish myself as an independent investigator during this award period by developing my research under the mentorship of outstanding physicians and researchers. The support from my mentors and my institution will contribute to a special environment for promoting the success of my research and career development. This effort will specifically involve my primary mentor, Dr. James Russell of University of Maryland School of Medicine, and co-mentors Dr. David Ginty of Harvard Medical School and Dr. Michael Polydefkis of Johns Hopkins University. The career development plan will build on my strong background in morphologic analysis of the nervous system, adding didactic training and research experiences in related disciplines. My overall career goal is to become an outstanding physician scientist in the field of sensory nervous system and related disorders. The Mentored Clinical Scientist Development Award will allow me to achieve this goal by providing dedicated time and resources for laboratory work and training activities. It will also provide me with an opportunity to develop the necessary skills to become an independent researcher. In this application, I propose to use mouse models to study the role of skin-derived BDNF in the maintenance of TrkB-expressing cutaneous sensory receptors and to characterize its mechanism in mediating the protective effect of Nicotinamide Riboside against diabetic neuropathy. The work highlights the importance of skin-derived BDNF in sensory nerve protection and the potential of Nicotinamide Riboside as a novel therapeutic agent for diabetic neuropathy.